Heritable, differential gene expression in pre-implantation embryos from rats with endometriosis and their daughters

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Endometriosis, which affects millions of women, is a condition where the uterine lining grows outside of the uterus and is associated with subfertility and pain. One cause of this subfertility is decreased embryo quality. Endometriosis has also been implicated to be heritable. Due to the ethical limitations of experimentation with human embryos, a rat model of surgically-induced endometriosis (Endo) along with controls (Sham) were used to study the effect on embryo development. Embryos collected from Endo and Sham rats (F1 generation) were of similar quantity and quality. Analysis of gene expression in F1 Endo embryos found several signaling pathways to be disrupted including an increase in the cell death pathway. To examine the heritability of the expression changes, daughters of Endo rats were generated. These rats had delayed puberty but their embryos (F2 Endo) collected were of similar quality and quantity as controls (F2 Sham). Similar gene expression changes as seen in the F1 Endo were found for two genes analyzed in F2 Endo embryos. This would suggest that the changes are heritable. This heritability could be a result of incorrect DNA methylation, which is a mark on the DNA which can affect gene expression levels. No DNA methylation differences were found in F1 or F2 embryos for the genes studied, although further studies are needed. These data confirm that some gene expression changes are heritable and future studies may reveal a treatment to prevent these anomalies during embryo development.--From public.pdf